Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Colchicine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1980

Elevated colchicine sensitivity of dermal lymphocytes in mycosis fungoides.

Lymphocytes in chronic lymphocytic leukaemia and in other malignant lymphomas exhibit an extreme sensitivity to colchicine and are cytolysed in vitro by 10(-6) M colchicine. This characteristic can be quantified with the colchicine sensitivity index which is used for diagnostic purposes. We have demonstrated that lymphocytes liberated from skin infiltrates in mycosis fungoides (6 patients) show an elevated colchicine sensitivity of 44 (p < 0.01); in contrast, the index of lymphocytes isolated from dermal infiltrates of reactive inflammatory dermatoses (9 patients) is low, being only 23. Determination of the colchicine sensitivity index can be helpful in the diagnosis of mycosis fungoides.

Adult↗
PubMed1981

Suppression of DNCB-induced irritant dermatitis by colchicine.

In vivo effects of colchicine on DNCB-induced primary irritant dermatitis in guinea-pigs were investigated with simultaneous evaluation of in vitro chemotactic activity of polymorphonuclear leukocytes (PMNs). Colchicine, 125, 250 and 500 microgram/kg, was injected intraperitoneally 1 hour prior to the painting of 20 microliter of 10% DNCB in acetone on shaved dorsum of the animals. In the control animals, erythema and induration were maximum and dermal PMN infiltration was most intense at 24 hours. In the colchicine-treated animals, induration--but not erythema--was reduced, with sparse dermal PMN infiltration. In vitro chemotaxis of PMNs from cardiac blood to LPS-treated serum using Boyden chamber techniques revealed maximal suppression of the activity in the colchicine injected animals at 12 hours. It is suggested that the reduced induration and decreased infiltration of PMNs in the inflammatory tissue in the colchicine-injected animals are caused by prior suppression of locomotion of PMNs in the peripheral blood.

Animals↗
PubMed1983

Retinal atrophy induced by intravitreous colchicine.

Colchicine is known to inhibit axoplasmic transport in ganglion cells. Previous studies have shown considerable, but largely reversible, retinal changes after low dosages of intravitreal colchicine in experimental animals. In the present study, the effects of 1.0 to 100 micrograms of intravitreal colchicine in monkeys were studied by ophthalmoscopy, light microscopy, and electron microscopy. Optic atrophy was ophthalmoscopically evident within 4 weeks after a single dose of 10 micrograms or more. Morphologic changes included progressive swelling of retinal neurons, accumulation of a fibrillogranular material, displacement of organelles, and loss of microtubules. Plasmalemmal rupture was observed in ganglion cells and in photoreceptors after as little as 1 microgram of colchicine. Relative sparing of the cone cells was noted. The retina of monkeys appears to be more sensitive to intravitreal colchicine than that of certain lower animals.

Animals↗
PubMed1980

Induction of prostaglandin E release from macrophages by colchicine.

Rat peritoneal macrophages released high amounts of prostaglandin E (PGE) when treated in vitro with 10(-7) to 10(-4) M colchicine. PGE production occurred after a lag period of 4 hr and proceeded at a constant rate for more than 24 hr. Lymphocytes could not be stimulated to PGE release by colchicine. Disaggregation of microtubules appeared to be an essential event, since lumicolchicine was inactive and addition of heavy water (D2O) abolished colchicine-induced PGE formation. Cytochalasin B (5 microgram/ ml) did not interfere with PGE production by colchicine during the initial 12 hr, but thereafter it gave rise to an activity capable of degrading or converting newly synthesized PGE. Although details of the mechanisms by which colchicine in association with disrupted microtubules may induce PGE release remain unclear, these observations suggest that components of the cytoskeleton may efficiently influence the biosynthesis of prostaglandins.

Animals↗
PubMed1981

Inhibition of intestinal secretion in rats by colchicine and vinblastine.

The role of microtubules in small intestinal electrolyte secretion was investigated in rats by testing the effects of colchicine and vinblastine, both of which inhibit microtubule assembly. In the intact rat, intraperitoneal injection of colchicine (5 mg/kg) inhibited cholera toxin and prostaglandin-stimulated secretion without inhibiting their effects on adenylate cyclase or cAMP concentration. Pretreatment with colchicine had no effect on fluid transport in the absence of secretory stimuli. When added to rat ileum in vitro, colchicine reduced by 60% the short-circuit current (Isc) response to dibutyryl cAMP added 4 h later, whereas its structural isomer, lumicolchicine, which does not inhibit microtubule assembly, was ineffective. Vinblastine reduced by 55% the Isc response to dibutyryl cAMP and theophylline added 2 h later. Two hour pretreatment with vinblastine also reduced by 40% the Isc response to the cholinergic agonist, carbamylcholine, a Ca-dependent secretory stimulus which does not increase cAMP concentration. In contrast to their antisecretory actions, neither colchicine nor vinblastine inhibited glucose-stimulated active Na absorption. These results suggest a role for microtubules in active electrolyte secretion in the small intestine.

Adenylyl Cyclases↗
PubMed1981

Correction of a suppressor cell deficiency in familial Mediterranean fever by colchicine.

We have previously reported a suppressor cell deficiency in four patients with familial Mediterranean fever (FMF). Since colchicine prevents FMF attacks, we tested the effect of colchicine (1 mg twice daily) on the suppressor cell function in three of these FMF patients. Proliferation of phytohaemagglutinin-stimulated responder cells co-cultured with concanavalin A-induced suppressor cells was measured. The three FMF patients' means (+/- s.e.m.) percentage suppression of normal responder cells was markedly low before treatment (6 +/- 2) but significantly (P less than 0.001) increased during colchicine treatment (41 +/- 5) to levels similar to normal volunteers' mean percentage suppression (44 +/- 3). Colchicine corrected their suppressor cell deficiency and prevented FMF attacks during the 15 months of treatment. These findings support the hypothesis that there may be an association between these three patients' suppressor cell deficiency and the pathogenesis of their disease. Furthermore, colchicine may be potentially useful in treating patients with other diseases associated with a suppressor cell deficiency.

Adult↗
PubMed1984

Binding of colchicine to beef brain tubulin: influence of methodology on binding constants.

We have evaluated the effects that methodology (incubation time, concentration of beef brain tubulin) have on the measurement of the interaction of tubulin with colchicine. The results show that, with DEAE filter paper assay, binding is maximal for 3 hr of incubation at 37 degrees C, and for low concentrations of tubulin (0.05 mg/ml). In these conditions binding constants determined with SCATCHARD plot are: constant of dissociation (KD) of complex tubulin-colchicine equal to 9.8 X 10(-7) M and stechiometry equal to 0.57 mole of colchicine bound for 1 mole of tubulin dimer. Competition of drugs with colchicine binding site may be evaluated with this methodology. IC50 and affinity constants (Ki) of podophyllotoxin, a competitive inhibitor of colchicine-binding determined with these experimental conditions were 1.3 X 10(-6) M and 1.1 X 10(-6) M, respectively.

Animals↗
PubMed1984

Colchicine therapy for refractory idiopathic thrombocytopenic purpura.

Fourteen patients with idiopathic thrombocytopenic purpura (ITP) refractory to splenectomy and corticosteroids (prednisone, 1 to 2 mg/kg of body weight per day) received at least 1.2 mg of oral colchicine daily for a minimum of two weeks. Three patients had complete responses and one had a partial response (response rate, 29%). Responses were evident within two weeks of commencing therapy. Only the patient with a partial response was receiving concomitant therapy, a stable dose of prednisone. Responsiveness to colchicine did not seem to correlate with responsiveness to vincristine sulfate. Side effects of colchicine therapy were mild and complications did not occur. A possible mechanism of action for colchicine in ITP is decreased clearance of opsonized platelets secondary to inhibition of microtubule-dependent events in macrophages. Colchicine is useful in the treatment of ITP resistant to standard treatment.

Administration, Oral↗
PubMed1984

Limited proteolysis of tubulin and the localization of the binding site for colchicine.

Limited proteolysis of porcine brain tubulin with trypsin resulted in a gradual loss of its colchicine binding activity as well as its ability of assembly into microtubules. The analysis of the tryptic degradation products showed a preferential proteolysis of alpha-tubulin subunit. This enzymatic proteolysis cleaved tubulin in one major site producing fragments of 36,000 and 16,000 daltons, the smaller polypeptides containing the carboxyl-terminal residue as shown by 14C tyrosination . However, proteolysis after incubation with 1 X 10(-3) M colchicine resulted in formation of the indicated fragments plus a 41,000-dalton fragment and smaller size peptides indicating the drug induces a second cleavage site closer to the carboxyl-terminal alpha-tubulin. Preincubation of tubulin with [3H]colchicine followed by proteolysis and separation of the fragments by Sephadex G-75 chromatography showed radioactive colchicine associated with the 16,000-dalton fragment and to the smaller size peptides resulting from digestion in the presence of the drug. The data indicate a localization of the colchicine-binding site in the 16,000-dalton segment containing the COOH-terminal region of alpha-tubulin subunit.

Animals↗
PubMed1983

Kinetics of amyloid deposition. II. The effects of dimethylsulfoxide and colchicine therapy.

Amyloid (AA) protein, when deposition begins, is deposited in two stages--a rapid deposition period of 2 weeks and a plateau stage. The effect of dimethylsulfoxide (DMSO) and colchicine therapy on the kinetics of amyloid deposition was dependent on the stage of the disease at which therapy began. If given during the rapid deposition period, colchicine delayed the increase in amyloid but did not abolish it. Eventually, splenic and liver amyloid reached the level seen in untreated animals. On the other hand, DMSO given during the rapid deposition period led to significant resorption of both splenic and liver amyloid. By contrast, colchicine and DMSO given after the rapid deposition period were essentially without effect in promoting amyloid resorption. These results correlated well with the serum levels of SAA, the putative AA precursor. Colchicine given during the period of rapid AA deposition caused a transient decline in SAA levels, which eventually returned to levels seen in untreated animals. DMSO given during the rapid deposition period rapidly abolished the high SAA levels and maintained it at a level seen in normal animals. Both colchicine and DMSO therapy, if instituted after the rapid amyloid deposition period, failed to reduce SAA levels significantly below that of untreated controls.

Amyloid↗
PubMed1983

Autoradiographic study of colchicine inhibition of DNA synthesis and cell migration in hairless mouse epidermis in vivo.

In vivo effects of colchicine on mitotic counts, DNA synthesis, and cell migration time were investigated in hairless mouse epidermis. [H3]TdR was used to examine DNA synthesis and measure the transit time. We found that colchicine (at a dose of 50 micrograms/25 g body weight) caused mitotic arrest, but had no effect on the number of cells in S phase during the first 4 hr after injection. Colchicine reduced the number of cells in S phase in normal epidermis during the 16-30 hr after injection, but the effect was no longer seen at 42 hr post injection. A similar depression in S-phase cell counts appeared in UVR-stimulated hyperplastic epidermis by 48 hr after injection of colchicine. In addition, migration of [H3]TdR-labelled cells from the basal layer to the superficial layers in UVR-stimulated hyperplastic epidermis was disturbed by colchicine injection. The delay in movement was not seen during the first 24 hr, but appeared by 48 hr after injection.

Animals↗
PubMed1983

[Expression of transformation characters in colchicine-resistant tumor cells].

Malignancy and anchorage independence of Djungarian hamster tumor cell lines resistant to different doses (0.1-5.0 micrograms/ml) of colchicine were studied. The clones with low colchicine resistance (15-20-fold) did not differ in tumorigenicity from parental cells. The TD50 for highly colchicine-resistant cells (200-800-fold) was several orders of magnitude higher than that for wild-type cells. Colchicine resistance did not affect the expression of the cells anchorage independence. The cloning efficiency in a semi-solid medium was the same both for colchicine-resistant cell lines and wild-type cells.

Animals↗
PubMed1983

[3H-colchicine accumulation in a mixed culture of colcemide-resistant and -sensitive cells].

Colchicine accumulation was studied in cell monolayer formed by colchicine-sensitive mouse normal fibroblasts and colchicine-resistant cells L-53. Accumulation of 3H-colchicine in the mixed culture of these cells after a 2 hours incubation approached 63% of the total radioactivity in pure cultures of fibroblasts and L-53 cells. Colchicine binding in pure culture of normal fibroblasts somewhat decreased when cell density increased. The results obtained are compatible with the present models of intercellular communication and provide evidence of metabolic cooperation between cells sensitive and resistant to mitostatics.

Animals↗
PubMed1980

In vivo and in vitro effects of colchicine and vinblastine on the secretory process of antibody-producing cells.

The sensitivity of the secretory process of antibody-synthesizing cells to microtubule-binding drugs, colchicine and vinblastine sulfate, was studied. Rats were immunized by footpad injections of horseradish peroxidase, and the popliteal lymph nodes were removed at various times after injection. Both in vivo effects of colchicine and in vitro effects of colchicine and vinblastine were studied. Quantitative data were obtained with in vitro drug-treated cells by labeling with L-3H-leucine and by measuring the secreted and the cytoplasmic immunoglobulins. It was found that inhibition of immunoglobulin secretion was about 78% and 93% by colchicine and vinblastine, respectively. the results obtained with the latter drug were more difficult to interpret because it also inhibited the biosynthesis of total proteins, and particularly that of immunoglobulins. Immunocytochemical studies of the in vivo and in vitro drug-treated cells performed by light and electron microscopy showed that in antibody-containing cells the Golgi area was often occupied by dilated antibody-containing vesicles, probably derived from the Golgi apparatus. In a few of these cells it was observed that antibody-containing rough endoplasmic reticulum was markedly dilated. the above results demonstrate that both microtubule-binding agents, colchicine and vinblastine, are potent inhibitors of the secretory process of plasma cells and seem to indicate that a correlation may exist between ultrastructural changes and inhibition of secretion.

Animals↗
PubMed1981

Familial Mediterranean fever associated with menstruation. Efficacy of intermittent colchicine therapy.

The majority of patients with familial Mediterranean fever have a random pattern of attacks without a clear prodrome. Continuous prophylaxis with colchicine has been shown to reduce the frequency of attacks. It is generally considered undesirable, however, to expose young patients to the potential adverse effects of continuous colchicine prophylaxis. The alternative of intermittent short courses of colchicine during acute attacks is often ineffective in patients without a clear prodrome. Case reports of patients with a pattern of attacks occurring 12-24 hours after the onset of menstrual bleeding have appeared. Such patients should be ideal candidates for intermittent colchicine therapy. A review of the literature reveals that a consistent pattern of attacks closely following the onset of menstruation is not uncommon. Such a patient is described who has responded completely to short courses of colchicine begun at the first sign of menstrual bleeding.

Adult↗
PubMed1981

A fluorescence stopped flow study of colchicine binding to tubulin.

The kinetics of colchicine binding to tubulin has been studied, using a fluorescence stopped flow. The measurements of Garland (Garland, D. L. (1978) Biochemistry 17, 4266-4272) have been extended to high colchicine concentrations and different temperatures. The appearance of fluorescence is biphasic. Both phases depend in a nonlinear way on colchicine concentration. The presence of colchicine dimers at these concentrations has been taken into account. The fast phase is analyzed as a two-step mechanism. The thermodynamic parameters of the fast initial binding, and the activation energy of the slow conformational change, have been determined. The relative magnitude of the slow phase depends on temperature. It is interpreted as a slow preequilibrium between two tubulin conformers. The effect of the microtubule-associated proteins on the different processes is studied. The binding of colchicine to tubulin ring-like oligomers is discussed.

Animals↗
PubMed1981

The role of morphological and functional changes in adrenergic nerves for the development of colchicine-induced supersensitivity in the rat vas deferens.

Local application of colchicine to the hypogastric plexus produced degenerative changes in about 40% of adrenergic nerve endings and a decrease in the neuromuscular transmission in the rat vas deferens. Unlike after denervation, both decreases in the number of normal nerve terminals and neuromuscular transmission induced by colchicine were incomplete and reversible. Although the time course of these changes was apparently related to that of the development of supersensitivity after colchicine treatment, the degeneration of adrenergic nerves does not seem to be an essential factor for the manifestation of colchicine-induced supersensitivity which is quantitatively and qualitatively identical to that induced by denervation. It is suggested that some neurotrophic factor(s) may contribute to the control of responsiveness of the smooth muscle and that the denervation-like supersensitivity is induced by colchicine through an interference of axonal transport in adrenergic nerves.

Animals↗
PubMed1995

Derivatives of colchicine preferentially taken up by the liver: an approach to the treatment of liver fibrosis.

The distribution in the mouse of colchicine and of two colchicine derivatives, namely formylcolchicine/formylated serum albumin (FC/FTSA) and formylcolchicine/lactosaminated serum albumin (FC/LASA), was studied. The presence of radioactivity after the intravenous injection of labelled colchicine or of its derivatives was determined in liver, small intestine, kidney and blood. The radioactivity of the derivatives was better retained than that of colchicine. The derivatives accumulated in the liver to a much greater extent than colchicine, but were scarcely present in the gut. Tropism towards the liver might be important for the use of FC/LASA and FC/FTSA to control liver fibrosis.

Animals↗